GSTT1 and GSTM1 polymorphisms and prostate cancer risk in Asians: a systematic review and meta-analysis

Abstract

Glutathione S-transferases (GSTs) enzymes are involved in conjugation of electrophilic compounds to glutathione, and glutathione S-transferase T 1 (GSTT1) and glutathione S-transferase M 1 (GSTM1) polymorphisms have been implicated as risk factors for prostate cancer. We conducted a systematic review and meta-analysis to define the effect of GSTM1 and GSTT1 null genotypes on prostate cancer risk in Asians. We searched the PubMed and Wanfang Medical databases to identify published case–control studies investigating the associations of GSTM1 and GSTT1 null genotypes with risk of prostate cancer in Asians. Heterogeneity was assessed using Cochran’s Q statistic and odds ratios (OR) with corresponding 95 % confidence intervals (95 % CI) from individual studies were pooled using fixed or random effects models according to the heterogeneity. There were 18 studies (2,046 cases, 2,876 controls) on GSTM1 polymorphism, 15 studies (1,677 cases, 2,431 controls) on GSTT1 polymorphism, and 6 studies (675 cases, 853 controls) on GSTM1/GSTT1 interaction analysis. Overall, GSTM1 null genotype was significantly associated with increased risk of prostate cancer in Asians (random effects OR 1.80, 95 % CI 1.48–2.18, P < 0.001), and GSTT1 null genotype was also significantly associated with increased risk of prostate cancer in Asians (random effects OR 1.40, 95 % CI 1.10–1.80, P < 0.001). In addition, the GSTM1/GSTT dual null genotype was associated with higher risk of prostate cancer in Asians (random effects OR 2.14, 95 % CI 1.59–2.89, P = 0.007). In conclusion, GSTM1 and GSTT1 null genotypes are associated with increased risk of prostate cancer in Asians, and GSTM1 and GSTT1 null genotypes are risk factors for the development of prostate cancer.

The association of glutathione S-transferase polymorphisms in patients with osteosarcoma: evidence from a meta-analysis

“…; Liu et al . ). In addition, the meta‐analysis also demonstrated the GSTM1 and GSTT1 null genotypes are associated with an increased risk of nasopharyngeal cancer (Murthy et al .…”

“…Meanwhile, mounting evidence by meta-analysis also shows that glutathione S-transferase polymorphisms is associated with risk of various diseases, particularly cancer [e.g. type 2 diabetes mellitus (Tang et al 2013), gastric cancer , hepatocellular carcinoma , prostate cancer (Hu et al 2013;Liu et al 2013) and nasopharyngeal cancer (Murthy et al 2013)]. The accumulated evidence proved the obvious associations of GSTM1 and GSTT1 polymorphisms with an increased risk of type 2 diabetes mellitus (Tang et al 2013).…”

“…The GSTT1 null genotype contributes to an increased risk of HCC in East Asians and that interaction between unfavourable GSTs genotypes may exist . The available data suggested that GSTM1 and GSTT1 null genotypes are associated with increased risk of prostate cancer in Asians, and GSTM1 and GSTT1 null genotypes are risk factors for the development of prostate cancer (Hu et al 2013;Liu et al 2013). In addition, the meta-analysis also demonstrated the GSTM1 and GSTT1 null genotypes are associated with an increased risk of nasopharyngeal cancer (Murthy et al 2013).…”

Interaction between GSTT1 and GSTP1 allele variants as a risk modulating-factor for autism spectrum disorders

“…Several of the GST family subgroup genes, including GST mu 1 ( GSTM1 ), GST pi 1 ( GSTP1 ), and GST theta 1 ( GSTT1 ), are highly polymorphic (Loktionov et al, 2001). Sequence variation in these genes has also been associated with an increased or decreased risk for several cancers and chronic diseases, including colorectal cancer (Loktionov et al, 2001), esophageal cancer (Sharma et al, 2013), renal cell carcinoma (Cheng, You, & Zhou, 2012; Yang et al, 2013), acute leukemia (Ye & Song, 2005), prostate cancer (Harries, Stubbins, Forman, Howard, & Wolf, 1997; Kote-Jarai et al, 2001; Liu, Liu, Ran, Shang, & Li, 2013; Safarinejad, Shafiei, & Safarinejad, 2011; Taioli et al, 2011; Wei et al, 2013), type-2 diabetes mellitus (Dadbinpour, Sheikhha, Darbouy, & Afkhami-Ardekani, 2013; Ramprasath et al, 2011), asthma (Tamer et al, 2004), and neurodevelopmental disorders such as ASD (Buyske et al, 2006). The variants in GSTM1 and GSTT1 examined here are insertion-deletion polymorphisms, and the homozygous deletions or null genotypes indicate that activities or functionality of these genes are reduced or interrupted completely (Ye, Song, Higgins, Pharoah, & Danesh, 2006).…”

The Role of the Clinical and Molecular Assays in Prostate Cancer Detection

“…Several genetic polymorphisms and total or partial deletions of GST family (GSTM1, GSTT1, GSTM3, GSTPI, and GSTZ1) have been identified that associated with a reduction of enzymatic activity [24]. The previous studies have suggested that individuals with null genotypes of GSTs may be unable to inactivate electrophilic carcinogens efficiently and higher risk for prostate cancer [25]. An additional finding was that GSTM1 null genotypes were significantly 45.5% higher in cancer and BPH group compare with normal men.…”